Methods and compositions for minimally invasive capsular augmentation of canine coxofemoral joints

ABSTRACT

The present technology relates to methods and devices for augmenting the canine coxofemoral joint. In particular, methods for augmenting the capsule of the canine coxofemoral joint are provided. In some embodiments, augmentation can be performed by injecting an implantable device comprising a biodegradable matrix and microparticles into the capsule. In some embodiments, augmentation can be performed by imbricating an implantable device comprising a biodegradable matrix and microparticles at the capsule.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No.12/398,124, filed Mar. 4, 2009, entitled “Methods and Compositions forMinimally Invasive Capsular Augmentation of Canine Coxofemoral Joints,”which claims priority to U.S. Provisional Application No. 61/034,118,filed Mar. 5, 2008, entitled “A Device and Method for Minimally InvasiveCapsular and Augmentation for Canine Coxofemoral Joint.” The disclosuresof all of the above-referenced prior applications, publication, andpatents are considered part of the disclosure of this application, andare incorporated by reference herein in their entirety.

FIELD OF THE INVENTION

The present technology relates to the field of veterinary medicine. Inparticular, methods and devices are provided for augmenting the capsuleof the canine coxofemoral joint.

BACKGROUND

Hip dysplasia is a common problem in veterinary practice, accounting forup to 30% of canine orthopedic cases (Richardson D. C. “The role ofnutrition in canine hip dysplasia.” Vet Clin North Am Small Anim. Pract.1992; 22: 529-540). The frequency of the disease varies among breeds andcan be as high as 70.5% in bulldogs and 48.2% in St. Bernards (Corley E.A, Keller G. G. “Hip Dysplasia: A Progress Report and Update.” Columbia,Mo.: Orthopedic Foundation of Animals 1993 (suppl)). Male and femaledogs are affected with equal frequency, in contrast to the disease inhumans, where 80% of cases are female (Committee on Quality Improvement,Subcommittee on Developmental Dysplasia of the Hip “Clinical PracticeGuideline: Early Detection of Developmental Dysplasia of the Hip”Pediatrics (2000) 105: 896-905).

The canine coxofemoral joint is a ball and socket joint, where thefemoral head meets the socket of the acetabulum. In chronic canine hipdysplasia, the joint becomes deformed where the femoral head is subluxedout of the joint resulting in significant pain, restricted range ofmotion, and accelerated osteoarthritic changes of the joint.

Treatment for canine hip dysplasia can include total hip replacement.Total hip replacement has become one of the most successful proceduresutilized in the treatment of canine hip dysplasia, and associateddisorders such as coxarthrosis; severe osteoarthritis, chronicsubluxation, avascular necrosis, and fracture dislocation. The typicalminimum age for total hip replacement is approximately 10 months and/ora body weight of 35 pounds, and there appears to be no upper age limitfor total hip replacement (Olmstead M L. “Total hip replacement.” VetClin North Am Small Anim Pract 1987, 17, 943-955; Tomlinson J,McLaughlin R Jr. “Total hip replacement: The best treatment fordysplastic dogs with osteoarthrosis. Symposium on CHD: SurgicalManagement.” Vet Med 1996, 91, 118-124; and Olmstead M L. “Total hipreplacement in the dog.” Semin Vet Med Surg (Small Anim) 1987, 2,131-140). However, total hip replacement can lead to complications suchas aseptic loosening, chronic subluxation, nerve injury, infection,fracture of the acetabulum, fracture of the femoral stem or shaft,patella luxation, pulmonary embolism and death (Konde L J, et al.“Radiographic evaluation of total hip replacement in the dog.” VetRadiol 1982, 20, 98-106; Liska W D. “Femur fractures associated withcanine total hip replacement.” Vet Surg 2004, 33, 164-172; andMontgomery R D et al. “Total hip arthroplasty for treatment of caninehip dysplasia.” Vet Clin North Am Small Anim Pract 1992, 22, 703-719).

Despite expensive screening and breeding programs, the disease continuesto have a major economic and emotional impact on dog breeders andowners. Accordingly, there is a need for minimally invasive methods anddevices to treat hip dysplasia and associated disorders.

SUMMARY

The present technology relates to methods and devices for augmenting thecapsule of a canine coxofemoral joint. Some methods described herein caninclude the steps of identifying a subject in need of capsularaugmentation, delivering an implantable device to the capsule, in whichthe implantable device includes a biodegradable matrix and a pluralityof microparticles, and contacting the implantable device with at least aportion of the capsule.

In some methods for augmenting the capsule of a canine coxofemoraljoint, the implantable device can include a sheet. In some suchembodiments, the sheet can include fenestrations. More methods can alsoinclude anchoring the implantable device at the joint. In certainembodiments, the anchoring can be at one or more sites of the jointselected from the capsule, iliofemoral ligament, ischiocapsularligament, pubocapsular ligament, acetabular labrum, ligamentum teresfemoris, acetabulum, or femoral neck.

In some methods for augmenting the capsule of a canine coxofemoraljoint, delivering can include injecting the implantable device into oneor more sites of the capsule. In some such methods, one or more sitescan be selected from the capsule, iliofemoral ligament, ischiocapsularligament, pubocapsular ligament. acetabular labrum, and ligamentum teresfemoris. In more embodiments, the injecting can be into at least aportion of the stratum fibrosum of the capsule.

In some methods for augmenting the capsule of a canine coxofemoraljoint, contacting the implantable device with at least a portion of thejoint can include at least a portion of one or more sites selected fromthe capsule, iliofemoral ligament, ischiocapsular ligament, pubocapsularligament, acetabular labrum, and ligamentum teres femoris.

In some methods for augmenting the capsule of a canine coxofemoraljoint, the joint has undergone capsulotomy or partial capsulectomy.

In some methods for augmenting the capsule of a canine coxofemoraljoint, delivering includes percutaneous delivery. In some methods foraugmenting the capsule of a canine coxofemoral joint, deliveringincludes an open surgical procedure.

In some methods for augmenting the capsule of a canine coxofemoraljoint, the biodegradable matrix includes bovine collagen.

In some methods for augmenting the capsule of a canine coxofemoraljoint, the biodegradable matrix includes one or more materials selectedfrom albumin, gelatin, chitosan, hyaluronic acid, starch, cellulose,cellulose derivatives (e.g. methylcellulose, hydroxypropylcellulose,hydroxypropylmethylcellulose, carboxymethylcellulose, cellulose acetatephthalate, cellulose acetate succinate, hydroxypropylmethylcellulosephthalate), casein, dextrans, polysaccharides, fibrinogen, poly(D,Llactide), poly(D,L-lactide-co-glycolide), poly(glycolide),poly(hydroxybutyrate), poly(alkylcarbonate), poly(orthoesters),polyesters, poly(hydroxyvaleric acid), polydioxanone, poly(ethyleneterephthalate), poly(malic acid), poly(tartronic acid), polyanhydrides,polyphosphazenes, poly(amino acids), and copolymers thereof.

In some methods for augmenting the capsule of a canine coxofemoraljoint, the plurality of microparticles include a material selected fromthe group consisting of poly methacrylate, polymethyl methacrylate,hydroxapatite, powdered bone, and glass.

In some methods for augmenting the capsule of a canine coxofemoraljoint, the plurality of microparticles can be substantially sphericalwith a diameter less than 200 μm. In more embodiments, the plurality ofmicroparticles can be substantially spherical with a diameter less than100 μm.

In some methods for augmenting the capsule of a canine coxofemoraljoint, the implantable device can also include a bioactive agent. Inmore embodiments, the bioactive agent can include an agent selected fromthe group consisting of a local anesthetic, non-steroidalanti-inflammatory drug, antibiotic, and antineoplastic agent. In moreembodiments, the bioactive agent can include lidocaine.

In some methods for augmenting the capsule of a canine coxofemoraljoint, the implantable device can also include a substrate. In moreembodiments, the substrate can include a material selected from nylon,Dacron, and Teflon. In more embodiments, the substrate can be coatedwith the plurality of microparticles and the biodegradable matrix.

In addition to the methods described herein, also provided is a caninecoxofemoral joint including an implantable device, in which theimplantable device comprises collagen and microparticles.

In some embodiments, the collagen comprises bovine collagen.

In some embodiments, the microparticles are substantially spherical witha diameter less than 200 μm. In more embodiments, the microparticles aresubstantially spherical with a diameter less than 100 μm.

In some embodiments, the implantable device further comprises abioactive agent. In more embodiments, the bioactive agent comprises anagent selected from the group consisting of a local anesthetic,non-steroidal anti-inflammatory drug, antibiotic, and antineoplasticagent. In more embodiments, the bioactive agent comprises lidocaine.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a schematic of a canine coxofemoral joint (5). The jointincludes the femoral head (10), the acetabulum (20), pelvis (30), andcapsule (40).

FIG. 2 shows a schematic of a canine coxofemoral joint imbricated with acollagen mesh containing microparticles.

FIG. 3 shows a schematic of a canine coxofemoral joint injected with acollagen matrix containing microparticles.

DETAILED DESCRIPTION

The present invention relates to methods and devices for augmenting thecapsule of a canine coxofemoral joint. In particular embodiments,methods are provided that include identifying a subject in need ofcapsular augmentation, delivering an implantable device to the capsule,in which the implantable device includes a biodegradable matrix and aplurality of microparticles, and contacting the implantable device withat least a portion of the capsule are described. Such methods anddevices can be useful to treat canine hip dysplasia and relateddisorders.

In some embodiments, the implantable device can include a biodegradablematrix, such as collagen, and microparticles comprised of polymethylmethacrylate (PMMA). The device can be inserted at the caninecoxofemoral to augment the capsule. Without wishing to be bound to anyone theory, it is believed that the biodegradable matrix provides asubstrate for the host's fibroblasts to migrate into the device andinvoke a fibrotic response at the insertion site. In addition, themicroparticles may further invoke the host to secrete components of theextracellular matrix, including the host's own collagen, at the site ofinsertion. Thus the response to inserting such an implantable device atthe canine coxofemoral capsule can be that the host produces a fibrousmatrix at the site of insertion, thickening and tightening the capsule,and strengthening the joint. Moreover, as the host continues to producea fibrous matrix at the site of insertion, the tensile strength at thesite of insertion can increase with time. This is in contrast to hiprepairs such as arthroplasty, which tend to become weaker over a periodof time through loosening of cement, stem migration or sublimation, andinfection.

Referring to FIG. 1, the canine coxofemoral joint (5) includes thefemoral head (10) which is used for articulation of the joint. Theacetabulum (20) represents the concave portion of the coxofemoral jointand is part of the pelvis (30). The deep acetabulum is further extendedby a band of fibrocartilage surrounding its rim. This acetabular lip iscontinued as a transverse acetabular ligament in the ventral aspect ofthe femur and completes the circular restraint of the hip joint. Theligament of the head of the femur, also known as the teres ligament orround ligament, is a short, flat ligament that connects the center ofthe femoral head to the acetabular fossa. This ligament contributes tofemoral stability by retaining the femoral head within the acetabulumand in the adult dog provides some vascularity to the femoral head. Thecoxofemoral joint is surrounded by a fibrous joint capsule (40) that isconnected to the femur at the base of the neck and at the acetabulumjust around the acetabular lip. In chronic canine hip dysplasia, thejoint becomes deformed where the femoral head is subluxed out of thejoint. In such cases, the capsule of the coxofemoral joint can be one ofthe only restraining structures to maintain containment.

In some methods to augment a canine capsule (40), an implantable solidmesh described herein. Referring now to FIG. 2, for example, a collagenmesh (50) containing microparticles can be wrapped around the capsule ofa canine coxofemoral joint. The mesh can be imbricated to the capsule.Because the capsule may not be invaded, this method has the advantage ofbeing minimally invasive. Thus the veterinary surgeon can minimize herincision on the capsule, reducing blood loss, and minimizing articulardestruction, as compared to more invasive methods. Moreover, wrappingthe capsule with the mesh strengthens the joint two-fold. First, themesh provides tensile strength to the capsule, and second, the tensilestrength increases as the biodegradable collagen is replaced by thehost's collagen and secretions.

In other embodiments, the implantable device can be in the form of afluid gel or paste. Such devices can be injected into a coxofemoralcapsule. Referring to FIG. 3, the implantable devices described hereincan be injected into the capsule using a syringe (60). As will beapparent, methods including injecting the implantable device areparticularly advantageous because the treatment is minimally invasive.

The following description is directed to certain specific embodiments.However, the invention can be embodied in a multitude of different ways.Reference in this specification to “one embodiment” or “an embodiment”means that a particular feature, structure, or characteristic describedin connection with the embodiment is included in at least oneembodiment. The appearances of the phrase “in one embodiment,”“according to one embodiment,” or “in some embodiments” in variousplaces in the specification are not necessarily all referring to thesame embodiment, nor are separate or alternative embodiments mutuallyexclusive of other embodiments. Moreover, various features are describedwhich may be exhibited by some embodiments and not by others. Similarly,one or more features may be described for one embodiment which can alsobe reasonably used in another embodiment.

As used herein, “at least a portion” can refer to at least about 0.1%,1%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80,%, 90%, 99% , and 100%.

Some of the implantable devices described herein are adapted to promotea fibrotic response at a site of contact. As used herein, “fibroticresponse” or “fibrosis” can refer to the formation of fibrous tissue inresponse to medical intervention. Implantable devices which induce afibrotic response can do so through one or more mechanisms, for example,stimulating migration or proliferation of connective tissue cells, suchas fibroblasts, smooth muscle cells, and vascular smooth muscle cells;inducing production of extracellular matrix components, such ascollagen; promoting tissue remodeling; and inducing or promotingangiogenesis.

An implantable device can comprise one or more components that caninclude, for example, a plurality of microparticles, a biodegradablematrix, a bioactive agent, and/or a substrate. The following descriptionprovides embodiments of implantable devices and methods of using suchdevices.

In some embodiments, microparticles can promote a fibrotic response atthe site of implantation and provide a scaffold to promote connectivetissue deposition around the microparticles. Microparticles can bemicrospheres, and/or nanoparticles. As will be understood,microparticles may be small enough to be delivered to a site, forexample, by injection, but large enough to resist phagocytosis and thelymphatic and blood system from washing away any of the microparticles.As such, microparticles can have a diameter of greater than about 10 μm.In some embodiments, the microparticles can have a diameter betweenabout 20 μm to about 200 μm, a diameter between about 25 μm to about 100μm, or a diameter between about 30 μm to about 50 μm. The microparticlescan also be highly refined to limit any inflammation from smallerparticles, and to increase the roundness and smoothness of theparticles.

The microspheres can comprise an inert, histocompatible material, suchas glass, hydroxapatite, powdered bone, or a polymer. The polymer can becured and polymerized prior to implantation to reduce toxic orcarcinogenic potential of the monomers or cure agents. The inerthistocompatible polymer can be an acrylic polymer. The acrylic polymercan be a polymer of methacrylate or one of its esters, such as methylmethacrylate, ethyl methacrylate, n-butyl methacrylate, isobutylmethacrylate, lauryl methacrylate, and 2-ethylhexyl methacrylate or anycombination or copolymer thereof. In preferred embodiments,microparticles can comprise polymethylmethacrylate (PMMA). Someembodiments in the form of a gel pr paste are described in U.S. Pat. No.5,344,452, which is incorporated by reference in its entirety.

Microparticles can be porous or non-porous. Porous microparticlescontaining an additional agent may be used to deliver agents to the siteof implantation.

In some embodiments, the microparticles can be suspended in a suspensionagent. The suspension agent can be an aqueous or non-aqueous solution.The suspension agent can be of sufficient viscosity to promote thesuspension of the microparticles. The suspension agent can be, forexample, up to about 0.1%, 0.2%, 0.5%, 1.0%, 2.0%, 5.0%, 10%, 15%, 20%,30%, 40%, 50%, 60%, 70% and 80% by volume microparticles. The amount ofmicroparticles used is determined in part by other components of thesuspension agent, such as the carrier concentration, and the method ofimplantation, such as injection.

The suspension agent can also contain a polymer, which can behistocompatible, as a carrier. Such a carrier can be a biodegradablematrix. A biodegradable matrix can comprise a biodegradable polymer.Examples of biodegradable polymers include collagen, albumin, gelatin,chitosan, hyaluronic acid, starch, cellulose, cellulose derivatives(e.g. methylcellulose, hydroxypropylcellulose,hydroxypropylmethylcellulose, carboxymethylcellulose, cellulose acetatephthalate, cellulose acetate succinate, hydroxypropylmethylcellulosephthalate), casein, dextrans, polysaccharides, fibrinogen, poly(D,Llactide), poly(D,L-lactide-co-glycolide), poly(glycolide),poly(hydroxybutyrate), poly(alkylcarbonate), poly(orthoesters),polyesters, poly(hydroxyvaleric acid), polydioxanone, poly(ethyleneterephthalate), poly(malic acid), poly(tartronic acid), polyanhydrides,polyphosphazenes, poly(amino acids), and copolymers thereof (seegenerally, Ilium, L., Davids, S. S. (eds.) “Polymers in Controlled DrugDelivery” Wright, Bristol, 1987; Arshady R., “Preparation ofbiodegradable microspheres and microcapsules.” J. Controlled Release17:1-22, 1991; Pitt C. G., “The controlled parenteral delivery ofpolypeptides and proteins.” Int. J. Pharm. 59:173-196, 1990; Holland etal, “Polymers for Biodegradable Medical Devices. 1. The Potential ofPolyesters as Controlled Macromolecular Release Systems.” J. ControlledRelease 4:155-180, 1986).

In preferred embodiments, the biodegradable polymer can comprisecollagen. Collagen may allow for the separation of the microspheres toallow tissue ingrowth. The collagen can be in many types and forms, orin combinations thereof. For example, collagen can be Type I, II or III.Collagen can be native, denatured or cross linked. The various types andforms of collagen are described generally in Methods in Enzymol. (1982)82:3-217, Pt. A, incorporated by reference in its entirety. For example,collagen can be produced from animal derived tissues such as bovine orporcine hides, avian combs, human tissues such as cadaver skin or humancell cultures or through recombinant methods. In some embodiments, animplantable device can contain a collagen fully dissolved or insuspension. The solution can contain up to about 0.1%, 0.2%, 0.5%, 1.0%,2.0%, 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%,40%, 50%, 60%, 70%, or 80% (v/v) collagen content. The amount ofcollagen content in the solution is in part determined by the resultantviscosity, the percentage of other components such as microparticles andthe method of implantation, such as injection.

In particular embodiments, an implantable device comprises a collagenmatrix and microparticles. An example of a commercially availablematerial that may be used in some embodiments includes ARTEFILL (ArtesMedical Inc.). ARTEFILL comprises PMMA microparticles suspended inbovine collagen.

Other examples of commercially available materials that have been usedfor tissue repair and cosmetic applications include bovine collagenproducts such as ZYDERM I, ZYDERM II, and ZYPLAST (each produced byAllergan Inc.); bioengineered human collagen products such as COSMODERMI, COSMODERM II, and COSMOPLAST (Allegan Inc.); and porcine collagenproducts such as EVOLENCE (Ortho-McNeil-Janssen Pharmaceuticals, Inc.).More examples of collagen products include collagen meshes such asINSTAT (Johnson & Johnson), and composite collagen meshes such asALLODERM (Lifecell Corp.), as well as collagen sponges such as SURGIFOAM(Johnson & Johnson) and TERUDERMIS (Terumo Corp.).

Implantable devices described herein can include additional bioactiveagents. Bioactive agents can include any composition that is able toinvoke a biological response in a subject. A biological response caninclude, for example, responses to promote healing such as a fibroticresponse. Examples of bioactive agents that can induce a fibroticresponse include silk, talc, chitosan, polylysine, fibronectin,bleomycin. As will be understood, in some embodiments, themicroparticles can induce a fibrotic response. More examples ofbioactive agents include local anesthetics (e.g. lidocaine, bupivacaine,procaine, tetracaine, dibucaine, benzocaine, p-buthylaminobenzoic acid2-(diethylamino)ethyl ester HCl, mepivacaine, piperocaine, dyclonine,and opioids such as morphine, diamorphine, pethidine, codeine,hydrocodone, and oxycodone), non-steroidal anti-inflammatory drugs (e.g.ketoprofen, auranofin, naproxen, acetaminophen, acetylsalicylic acid,ibuprofen, phenylbutazone, indomethacin, sulindac, diclofenac,paracetamol, and diflunisal, Celecoxib, and Rofecoxib), antibiotics(e.g. clindamycin, minocycline, erythromycin, probenecid, andmoxifloxacin), and antineoplastic agents. Antineoplastic agents can haveantimicrobial activity at extremely low doses; examples includeanthracyclines (e.g. doxorubicin and mitoxantrone), fluoropyrimidines(e.g. 5-FU), folic acid antagonists (e.g. methotrexate), podophylotoxins(e.g. etoposide), camptothecins, hydroxyureas, and platinum complexes(e.g. cisplatin). In preferred embodiments, the implantable deviceincludes lidocaine. The concentration of lidocaine can be less thanabout 0.1%, 0.2%, 0.3%, 0.5%, 0.7%, 0.8%, 0.9%, 1%, and 5% by weight

Implantable devices described herein can include a substrate. Themicroparticles and/or biodegradable matrix can be embedded in thesubstrate. In some embodiments, the microparticles and/or biodegradablematrix can coat or wrap at least a portion of the substrate. Thesubstrate can comprise a non-biodegradable material such as, nylon,Dacron and Teflon. More examples of non-biodegradable materials that canbe used with the embodiments described herein include polyamides,polyolefins (e.g. polypropylene and polyethylene), polyurethanes,polyester/polyether block copolymers, polyesters (e.g. PET,polybutyleneterephthalate, and polyhexyleneterephthalate), polyestercloth (e.g. DACRON), polyester sheeting (e.g. MYLAR; DuPont), nylonmeshes, DACRON meshes (e.g. MERSILENE; Ethicon, Inc.), acrylic cloth(ORLON; DuPont), polyvinyl sponge (IVALON), polyvinyl cloth (VINYON-N),polypropylene mesh (MARLEX or BARD; CR Bard, Inc.; and PROLENE; Ethicon,Inc.), silicones, fluoropolymers (e.g. fluorinated ethylene propylene),and polytetrafluoroethylene (PTFE; e.g. TEFLON mesh and cloth; DuPont).

In some implementations, an implantable device can be a fluid,suspension, emulsion, microspheres, paste, gel, spray, aerosol, orsheet. With respect to sheets, the dimensions of a sheet can varyaccording to the application. Accordingly, sheets can be of varyingsizes, thicknesses, geometries and densities. For applications such ascapsular augmentation, the sheet can have a thickness of less than about1 mm, 2 mm, 3 mm, 4 mm, 5 mm, and 10 mm. As will be appreciated, a sheetcan be trimmed to the geometries and size appropriate to theapplication. In some embodiments, a sheet can be rectangular with alength sufficient to circumvent the capsule of a canine coxofemoraljoint. In some embodiments, a sheet can have a length and breadthsufficient to make contact with at least a portion of the capsule of acanine coxofemoral joint.

For sheet material, woven structures are advantageous, as well asmicroporous materials. The implantable device may be fenestrated topromote infiltration by the host into the sheet. Such meshes can act asa scaffold. The fenestrations may be formed in a variety of geometricshapes and sizes. Initially, a fenestrated implantable device may not beas strong as a solid sheet. However, because of the increased surfacearea and the potential for fibrovascular infiltration through thefenestrations, a fenestrated implantable device may ultimately bestronger than a solid sheet implant. The fenestrations may also be usedwith sutures or other fixing devices to attach the implantable device toa site, for example, the capsule of a canine coxofemoral joint.

An implantable device including a mesh can provide many importantadvantages. Some mesh implants may be only as strong as the tissue inwhich the mesh is integrated. However, without wishing to be bound byany one theory, it is believed that when the implant includesmicroparticles a fibrotic response is induced in the host. In such aresponse, the host's response for healing occurs especially quicklyalong the scaffold of the implant. The microparticles make this processoccur much faster than mesh implants without particles associatedtherewith. The body's inflammatory response to the mesh implant is suchthat fibrous tissue forms a capsule around the biological mesh, and,thus, provides stability and security in the repair.

As used herein “subject” can refer to an animal that can benefit fromthe methods and devices described herein. As will be understood by oneof skill in the art, “need” is not an absolute term and merely impliesthat the subject can benefit from the methods and devices describedherein. In preferred embodiments, the subject is a dog.

Augmentation of a coxofemoral joint may prevent, reduce, or treatvarious joint disorders. Disorders amenable to the methods andcompositions described herein can include, for example, hip dysplasia,osteoarthritis, coxarthrosis, and chronic subluxation. More examplesinclude chronic luxations, failed closed reductions, excessivepostreduction instability, intra-articular fractures, concurrent pelvicfractures, or other fractures of the affected limb that prevent closedreduction (Martini F. M. et al., “Extra-articular absorbable suturestabilization of coxofemoral luxation in dogs.” Vet Surg 30: 468-475(2001), incorporated by reference in its entirety). Moreover, thedevices and methods described herein can also be utilized in associationwith other methods well known in the art to promote stabilization of hipluxation (see generally, Johnson A. L. and Dunning D. Atlas oforthopedic surgical procedures of the dog and cat. Chapters 15-18(2005), incorporated by reference in its entirety).

A subject can be identified by various methods, including, for example,by x-ray or a test that requires manipulation of the hip joint intostandard positions well known in the art (see generally, Slatter, D.,Textbook of Small Animal Surgery, Chapter 144 (2002), incorporated byreference in its entirety).

In addition, the methods and compositions can be used prophylacticallyto prevent or reduce future damage or degeneration of a joint. Subjectsthat may benefit from treatment can include particular types of dogsthat may be more susceptible to hip dysplasia, for example, larger dogsand particular breeds such as Golden Retrievers, Labrador Retrievers,German Shepherds, Bulldogs, and St Bernards. Also, dogs with hip jointlaxity may be susceptible to hip dysplasia and associated disorders.Such subjects may benefit from prophylactic treatment.

Various methods can be used to deliver an implantable device to asubject. In some embodiments, the method of delivery can be during anopen surgical procedure, microdisectomy, percutaneous procedure, and/orby injection. Where an implantable device comprises a gel, paste, liquidor fluid, the device can be delivered to a site at the coxofemoral jointby injection. As will be appreciated, the size of the needle used duringsuch injections will vary according to the subject, viscosity of theimplantable device, and application. For example, the needle can have agauge in the range of about 22 to 25, and length in the range of about1.5 to 3.0 inches. The volume injected can be less than about 0.1 ml,0.5 ml, 1.0 ml, 1.2 ml, 1.5 ml, 2.0 ml, 2.5 ml, 5 ml, 10 ml, 20 ml, and50 ml. Delivery can be to one of more sites at the coxofemoral joint sothat the implantable device contacts at least a portion of thecoxofemoral joint. Such sites may be intra-articular or extra-articular,and can include the capsule, the stratum fibrosum of the capsule, theiliofemoral ligament, ischiocapsular ligament, pubocapsular ligament,acetabular labrum, and ligamentum teres femoris.

Several techniques can be used to guide delivery during injection. Suchtechniques can include, for example, fluoroscopy, ultrasound, and/or theuse of anatomical landmarks only. In preferred embodiments, injectionsmay be with the aid of a fluoroscope. In such embodiments, theimplantable device can include a contrast dye to visualize delivery ofthe implantable device at the site of implantation.

Where an implantable device comprises a sheet, the sheet may bedelivered to a site at the coxofemoral joint during an open surgicalprocedure, microdisectomy, and/or percutaneous procedure. As usedherein, “sheet” can also refer to “mesh” in some instance. The sheet cancontact at least a portion of the coxofemeroal joint at one or moresites, for example, the capsule, the iliofemoral ligament,ischiocapsular ligament, pubocapsular ligament, acetabular labrum, andligamentum teres femoris. In some embodiments, a sheet can circumventthe coxofemoral joint, and in particular, the capsule of the coxofemoraljoint. In such embodiments, the sheet may be imbricated to the capsuleand stimulate tissue growth. It is envisioned that new tissue growthtightens the capsule, thus promoting containment and minimizingsubluxation at the joint.

Sheets can be attached at one or more sites at a coxofemoral joint. Suchsites will be apparent to a skilled artisan, and may include, thecapsule, iliofemoral ligament, ischiocapsular ligament, pubocapsularligament, acetabular labrum, ligamentum teres femoris, acetabulum, andfemoral neck. Sheets can be anchored to the joint by various methods.Examples include the use of sutures, screws, anchors, hooks, staples,pins, and darts with methods well known in the art.

In certain embodiments, the coxofemoral joint may include a defect, forexample, a partial capsulectomy, small capsulotomy, or largecapsulotomy. The sheet can span the defect and be attached to the jointto augment the compromised capsule, for example, at the capsule at theedges of the defect. In some embodiments, the sheet can be attached tothe defect. In addition, it is also envisioned that the devicesdescribed herein can be used where a coxofemoral joint has undergonecomplete capsulectomy. In such embodiments, a sheet can be utilized toreplace the capsule and attached to the acetabulum and femoral neck ofthe joint.

Various modifications to these examples may be readily apparent to thoseskilled in the art, and the principles defined herein may be applied toother examples without departing from the spirit or scope of the novelaspects described herein. Thus, the scope of the disclosure is notintended to be limited to the examples shown herein but is to beaccorded the widest scope consistent with the principles and novelfeatures disclosed herein. Accordingly, the novel aspects describedherein is to be defined solely by the scope of the following claims.

What is claimed is:
 1. A canine coxofemoral joint augmented with animplantable device, wherein said implantable device comprises collagenand microparticles.
 2. The canine coxofemoral joint of claim 1, whereinsaid collagen comprises bovine collagen.
 3. The canine coxofemoral jointof claim 1, wherein said microparticles are substantially spherical witha diameter less than 200 μm.
 4. The canine coxofemoral joint of claim 3,wherein said microparticles are substantially spherical with a diameterless than 100 μm.
 5. The canine coxofemoral joint of claim 1, whereinsaid implantable device further comprises a bioactive agent.
 6. Thecanine coxofemoral joint of claim 5, wherein said bioactive agentcomprises an agent selected from the group consisting of a localanesthetic, non-steroidal anti-inflammatory drug, antibiotic, andantineoplastic agent.
 7. The canine coxofemoral joint of claim 5,wherein said bioactive agent comprises lidocaine.